This application proposes a comprehensive effort to generate overlapping yeast artificial chromosome (YAC) clones stretching from the class II MHC locus HLA-DRb to the class I MHC genes as well as approximately 500-700 kb of previously unmapped DNA. A detailed restriction may of the cluster will be prepared and the newly cloned sequences will be analyzed for the presence of transcribed regions indicative of functional genes. In addition, probes derived at regular intervals along the cluster will be used to compare the structures of the MHC of individuals bearing disease-associated MHC extended haplotypes and normal individuals. The studies will permit a more complete analysis of the evolution of the MHC and may permit a better understanding of the function of the class III concerning the nature of extended MHC haplotypes of MHC-associated susceptibility to development of autominnume disease.